{"doi":"10.2337/db24-0083","title":"Effect of Weight Loss on Skeletal Muscle Bioactive Lipids in People With Obesity and Type 2 Diabetes","abstract":"Muscle sn-1,2-diacylglycerol (DAG) and C18:0 ceramide accumulation in sarcolemmal and mitochondrial compartments have been proposed to regulate muscle insulin sensitivity. Here, we evaluated whether weight loss-induced improvements in insulin sensitivity were associated with changes in muscle sn-1,2-DAG and ceramide content in people with obesity and type 2 diabetes. We measured skeletal muscle insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose tracer infusion, and skeletal muscle sn-1,2-DAG and ceramide contents by using liquid chromatography-tandem mass spectrometry after subcellular fractionation and DAG isomer separation in 14 adults with obesity and type 2 diabetes before and after marked (18.6 ± 2.1%) weight loss. Whole-body insulin sensitivity doubled after weight loss. Sarcolemmal sn-1,2-DAG and C18:0 ceramide contents after weight loss were not different from values before weight loss. In contrast, mitochondrial-endoplasmic reticulum (ER) C18:0 ceramide content decreased by ∼20% after weight loss (from 2.16 ± 0.08 to 1.71 ± 0.13 nmol/g, P < 0.005). These results suggest a decrease in muscle mitochondrial-ER C18:0 ceramide content could contribute to the beneficial effect of weight loss on skeletal muscle insulin sensitivity.","journal":"Diabetes","year":2024,"id":432460,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240810,"name":"Mihoko Yoshino","orcid":"0000-0003-4123-7699","position":1,"is_corresponding":false},{"id":267703,"name":"Gordon I. Smith","orcid":"0000-0003-0063-046X","position":2,"is_corresponding":false},{"id":256420,"name":"Rafael Calais Gaspar","orcid":"0000-0002-2208-3527","position":3,"is_corresponding":false},{"id":257346,"name":"Mario Kahn","orcid":null,"position":4,"is_corresponding":false},{"id":616311,"name":"Dmitri Samovski","orcid":"0000-0002-6860-6688","position":5,"is_corresponding":false},{"id":232241,"name":"Gerald I. Shulman","orcid":"0000-0003-1529-5668","position":6,"is_corresponding":false},{"id":55892,"name":"Samuel Klein","orcid":"0000-0001-7127-1156","position":7,"is_corresponding":false},{"id":783717,"name":"Max C. Petersen","orcid":"0000-0001-8646-2377","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T01:59:35.267142Z","pmid":"39264820","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}